TMPRSS4 is a novel type II transmembrane serine protease found at the cell surface that is highly expressed in pancreatic, colon and gastric cancer tissues. However, the biological functions of ...TMPRSS4 in cancer are unknown. Here we show, using reverse transcription-PCR, that TMPRSS4 is highly elevated in lung cancer tissues compared with normal tissues and is also broadly expressed in a variety of human cancer cell lines. Knockdown of TMPRSS4 by small interfering RNA treatment in lung and colon cancer cell lines was associated with reduction of cell invasion and cell-matrix adhesion as well as modulation of cell proliferation. Conversely, the invasiveness, motility and adhesiveness of SW480 colon carcinoma cells were significantly enhanced by TMPRSS4 overexpression. Furthermore, overexpression of TMPRSS4 induced loss of E-cadherin-mediated cell-cell adhesion, concomitant with the induction of SIP1/ZEB2, an E-cadherin transcriptional repressor, and led to epithelial-mesenchymal transition events, including morphological changes, actin reorganization and upregulation of mesenchymal markers. TMPRSS4-overexpressing cells also displayed markedly increased metastasis to the liver in nude mice upon intrasplenic injection. Taken together, these studies suggest that TMPRSS4 controls the invasive and metastatic potential of human cancer cells by facilitating an epithelial-mesenchymal transition; TMPRSS4 may be a potential therapeutic target for cancer treatment.
Aims
For the effective production of 146S particles, which determines foot‐and‐mouth disease (FMD) vaccine efficacy, we aimed to identify the optimal medium that is easy‐to‐use, productive and ...economically affordable for the large‐scale production of FMD vaccine.
Methods and Results
Nine combinations of cell growth media and replacement media were tested for virus propagation. Apart from the replacement strategy, we tested a simple addition strategy involving the addition of 30% v/v of fresh medium to the total spent medium using the Cellvento BHK‐200 (Vento). Unlike other tested media that produced poor yields of 146S particles when the spent media were not eliminated, Vento exhibited high productivity with the 30% addition strategy.
Conclusions
Considering its lower price and media consumption compared to those of other media that require media replacement, the 30% addition strategy of Vento is highly effective. Furthermore, owing to its simple application strategy, it makes the scale‐up process easy and helps in saving the time and labour involved in spent media removal.
Significance and Impact of the Study
Through the first comparative assessment of commercial media for the 146S particle recovery, this study suggests the best practical medium for the industrial‐scale production of FMD vaccines.
Background
While the clinical characteristics and outcomes of asthma‐chronic obstructive pulmonary disease (COPD) overlap (ACO) have been frequently compared with those of COPD or asthma, the ...prevalence and features of ACO in patients with severe asthma are unclear.
Objectives
Evaluation of the prevalence and clinical features of ACO using the Korean severe asthma registry.
Methods
At the time of registration, ACO was determined in patients with severe asthma by attending specialists. Patients were classified into ACO and non‐ACO groups, and the demographic and clinical characteristics of these two groups were compared.
Results
Of 482 patients with severe asthma, 23.7% had ACO. Patients in the ACO group were more likely to be male (P < .001), older (P < .001), and ex‐ or current smokers (P < .001) compared with those in the non‐ACO group. Patients in the ACO group had lower mean forced expiratory volume in 1 second (P < .001) and blood eosinophil percentage (P = .006), but higher blood neutrophil percentage (P = .027) than those in the non‐ACO group. The ACO group used more inhaled long‐acting muscarinic antagonist (P < .001), methylxanthine (P = .001), or sustained systemic corticosteroid (P = .002). In addition, unscheduled emergency department visits due to exacerbation were more frequent in the ACO group (P = .006).
Conclusion
Among patients with severe asthma, those with ACO were older, predominantly male, and were more likely to have a smoking history than those with asthma only. Patients with ACO used more systemic corticosteroid and had more frequent exacerbations related to emergency department visits than those with severe asthma only.
We found that about one‐fourth of patients with severe asthma was diagnosed with ACO by specialists. The most common reason for ACO diagnosis was smoking history. ACO patients were predominantly male, older, and had more smoking history compared with non‐ACO patients. ACO patients had higher blood neutrophil count, but lower lung function. ACO patients used more LAMA, methylxanthine, and systemic corticosteroid and had more frequent exacerbations related to ER visits compared with those with severe asthma only. Abbreviations: ACO, asthma‐COPD overlap; ER, emergency room; FEV1, forced expiratory volume in one second.
Background: This study was to devise a prognostic model for metastatic gastric cancer patients undergoing first-line chemotherapy. Patients and methods: A retrospective analysis was carried out on ...1455 gastric cancer patients, who received first-line chemotherapy from September 1994 to February 2005. Results: At multivariate level, poor prognostic factors were no previous gastrectomy P = 0.003; relative risk (RR), 1.191; 95% confidence interval (CI) 1.061–1.338, albumin <3.6 g/dl (P = <0.001; RR, 1.245; 95% CI 1.106–1.402), alkaline phosphatase >85 U/l (P = <0.001; RR, 1.224; 95% CI 1.092–1.371), Eastern Cooperative Oncology Group performance status of two or more (P = <0.001; RR, 1.690; 95% CI 1.458–1.959), the presence of bone metastases (P = 0.001; RR, 1.460; 95% CI 1.616–1.836), and the presence of ascites (P = <0.001; RR, 1.452; 95% CI 1.295–1.628). Of 1434 patients, 489 patients (34.1%) were categorized as low-risk group (zero to one factors), 889 patients (62.0%) as intermediate-risk group (two to four factors), and 56 patients (3.9%) as high-risk group (five to six factors). Median survival durations for low, intermediate, and high-risk groups were 12.5 months, 7.0 months, and 2.7 months, respectively. Conclusions: This model should facilitate the individual patient risk stratification and thus, more appropriate therapies for each metastatic gastric cancer patient.
We evaluated whether ELISPOT assay can predict tuberculosis (TB) development in kidney‐transplantation (KT) recipients with a negative tuberculin skin test (TST). All adult patients admitted to a KT ...institute between June 2008 and December 2009 were enrolled; TB development after KT was observed between June 2008 and December 2010. Isoniazid (INH) was given to those patients with positive TST or clinical risk factors for latent TB infection (LTBI). ELISPOT assay was performed on all patients, and TB development after KT was observed by a researcher blinded to the results of ELISPOT. A total of 312 KT recipients including 242 (78%) living‐donor KT were enrolled. Of the 312 patients, 40 (13%) had positive TST or clinical risk factors for LTBI and received INH; none developed TB after KT. Of the remaining 272 patients, 4 (6%) of 71 with positive ELISPOT assay developed TB after KT, whereas none of the 201 patients with negative (n = 171) or indeterminate ELISPOTs (n = 30) developed TB after KT (rate difference between positive and negative/indeterminate ELISPOT, 3.3 per 100 person‐years 95% CI 1.4–5.1, p<0.001). Positive ELISPOT results predict subsequent development of TB in KT recipients in whom LTBI cannot be detected by TST or who lack clinical risk factors for LTBI.
Positive results of an interferon‐gamma releasing assay anticipate the subsequent development of tuberculosis in kidney transplant recipients in whom latent tuberculosis infection cannot be detected by tuberculin skin test or who lack clinical risk factors for latent tuberculosis infection. See editorial by Torre‐Cisneros and Doblas on page 1769.
Abstract
Perovskite light-emitting diodes (PeLEDs) based on three-dimensional (3D) polycrystalline perovskites suffer from ion migration, which causes overshoot of luminance over time during ...operation and reduces its operational lifetime. Here, we demonstrate 3D/2D hybrid PeLEDs with extremely reduced luminance overshoot and 21 times longer operational lifetime than 3D PeLEDs. The luminance overshoot ratio of 3D/2D hybrid PeLED is only 7.4% which is greatly lower than that of 3D PeLED (150.4%). The 3D/2D hybrid perovskite is obtained by adding a small amount of neutral benzylamine to methylammonium lead bromide, which induces a proton transfer from methylammonium to benzylamine and enables crystallization of 2D perovskite without destroying the 3D phase. Benzylammonium in the perovskite lattice suppresses formation of deep-trap states and ion migration, thereby enhances both operating stability and luminous efficiency based on its retardation effect in reorientation.
Summary Background The role of adjuvant chemotherapy for patients with rectal cancer is controversial, especially when used after preoperative chemoradiotherapy. Fluoropyrimidine-based adjuvant ...chemotherapy, including fluorouracil and leucovorin, has been widely used; however, the addition of oxaliplatin to fluorouracil and leucovorin (FOLFOX), a standard adjuvant regimen for colon cancer, has not been tested in rectal cancer. We aimed to compare the efficacy and safety of adjuvant fluorouracil and leucovorin with that of FOLFOX in patients with locally advanced rectal cancer after preoperative chemoradiotherapy. Methods In this open-label, multicentre, phase 2, randomised trial, patients with postoperative pathological stage II (ypT3–4N0) or III (ypTany N1–2) rectal cancer after preoperative fluoropyrimidine-based chemoradiotherapy and total mesorectal excision were recruited and randomly assigned (1:1) via a web-based software platform to receive adjuvant chemotherapy with either four cycles of fluorouracil and leucovorin (fluorouracil 380 mg/m2 and leucovorin 20 mg/m2 on days 1–5, every 4 weeks) or eight cycles of FOLFOX (oxaliplatin 85 mg/m2 , leucovorin 200 mg/m2 , and fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2400 mg/m2 for 46 h, every 2 weeks). Stratification factors were pathological stage (II vs III) and centre. Neither patients nor investigators were masked to group assignment. The primary endpoint was 3-year disease-free survival, analysed by intention to treat. This study is fully enrolled, is in long-term follow-up, and is registered with ClinicalTrials.gov , number NCT00807911. Findings Between Nov 19, 2008, and June 12, 2012, 321 patients were randomly assigned to fluorouracil and leucovorin (n=161) and FOLFOX (n=160). 141 (95%) of 149 patients in the fluorouracil plus leucovorin group and 141 (97%) of 146 in the FOLFOX group completed all planned cycles of adjuvant treatment. Median follow-up was 38·2 months (IQR 26·4–50·6). 3-year disease-free survival was 71·6% (95% CI 64·6–78·6) in the FOLFOX group and 62·9% (55·4–70·4) in the fluorouracil plus leucovorin group (hazard ratio 0·657, 95% CI 0·434–0·994; p=0·047). Any grade neutropenia, thrombocytopenia, fatigue, nausea, and sensory neuropathy were significantly more common in the FOLFOX group than in the fluorouracil plus leucovorin group; however, we noted no significant difference in the frequency of these events at grade 3 or 4. The most common grade 3 or worse adverse events were neutropenia (38 26% of 149 patients in the fluorouracil plus leucovorin group vs 52 36% of 146 patients in the FOLFOX group), leucopenia (eight 5% vs 12 8%), febrile neutropenia (four 3% vs one <1%), diarrhoea (four 3% vs two 1%), and nausea (one <1% vs two 1%). Interpretation Adjuvant FOLFOX improves disease-free survival compared with fluorouracil plus leucovorin in patients with locally advanced rectal cancer after preoperative chemoradiotherapy and total mesorectal excision, and warrants further investigation. Funding Korea Healthcare Technology R&D Project (South Korean Ministry of Health and Welfare).
Monodisperse spherical Ni nanoparticles with diameters of 2 nm, 5 nm, and 7 nm were synthesized from the thermal decomposition of a Ni–oleylamine complex. Ni nanocrystal superlattices were generated ...via the controlled evaporation of solvent (see Figure). The nanoparticles were successfully used as catalysts for the Suzuki coupling reaction, and were readily oxidized to produce NiO nanoparticles.
To cite this article: Cheong HS, Park S‐M, Kim M‐O, Park J‐S, Lee JY, Byun JY, Park BL, Shin HD, Park C‐S. Genome‐wide methylation profile of nasal polyps: relation to aspirin hypersensitivity in ...asthmatics. Allergy 2011; 66: 637–644.
Background: In addition to the dysregulation of arachidonic acid metabolism in aspirin‐intolerant asthma (AIA), aspirin acetylsalicylic acid (ASA) exerts effects on inflammation and immunity; however, many of these effects are unknown.
Objective: The aim of the study was to evaluate the methylation status of whole genome in blood and polyp tissues with and without aspirin hypersensitivity.
Methods: Genome‐wide DNA methylation levels in nasal polyps and peripheral blood cells were examined by microarray analysis using five subjects with AIA and four subjects with aspirin‐tolerant asthma (ATA).
Results: In the nasal polyps of the patients with AIA, hypermethylation was detected at 332 loci in 296 genes, while hypomethylation was detected at 158 loci in 141 genes. Gene ontologic and pathway enrichment analyses revealed that genes involved in lymphocyte proliferation, cell proliferation, leukocyte activation, cytokine biosynthesis, cytokine secretion, immune responses, inflammation, and immunoglobulin binding were hypomethylated, while genes involved in ectoderm development, hemostasis, wound healing, calcium ion binding, and oxidoreductase activity were hypermethylated. In the arachidonate pathway, PGDS, ALOX5AP, and LTB4R were hypomethylated, whereas PTGES was hypermethylated.
Conclusion: The nasal polyps of patients with AIA have characteristic methylation patterns affecting 337 genes. The genes and pathways identified in this study may be associated with the presence of aspirin hypersensitivity in asthmatics and are therefore attractive targets for future research.
Objectives
Current prognostic systems for intrahepatic cholangiocarcinoma (IHCC) rely on surgical pathology data and are not applicable to a preoperative setting. We aimed to develop and validate ...preoperative models to predict postsurgical outcomes in mass-forming IHCC patients based on clinical, radiologic, and radiomics features.
Methods
This multicenter retrospective cohort study included patients who underwent curative-intent resection for mass-forming IHCC. In the development cohort (single institution data), three preoperative multivariable Cox models for predicting recurrence-free survival (RFS) were constructed, including the clinical-radiologic, radiomics, and clinical-radiologic-radiomics (CRR) models based on clinical and CT findings, CT-radiomics features, and a combination of both, respectively. Model performance was evaluated in the test cohort (data from five institutions) using Harrell’s C-index and compared with postoperative prognostic systems.
Results
A total of 345 patients (233, development cohort; 112, test cohort) were evaluated. The clinical-radiologic model included five independent CT predictors (infiltrative contour, multiplicity, periductal infiltration, extrahepatic organ invasion, and suspicious metastatic lymph node) and showed similar performance in predicting RFS to the radiomics model (C-index, 0.65 vs. 0.68;
p
= 0.43 in the test cohort). The CRR model showed significantly improved performance (C-index, 0.71;
p
= 0.01) than the clinical-radiologic model and demonstrated similar performance to the postoperative prognostic systems in predicting RFS (C-index, 0.71–0.73 vs. 0.70–0.73;
p
≥ 0.40) and overall survival (C-index, 0.68–0.71 vs. 0.64–0.74;
p
≥ 0.27) in the test cohort.
Conclusions
A model integrating clinical, CT, and radiomics information may be useful for the preoperative assessment of postsurgical outcomes in patients with mass-forming IHCC.
Key Points
• The radiomics analysis had incremental value in predicting recurrence-free survival of patients with intrahepatic mass-forming cholangiocarcinoma.
• The clinical-radiologic-radiomics model demonstrated similar performance to the postoperatively available prognostic systems (including 8th AJCC system) in predicting recurrence-free survival and overall survival.
• The clinical-radiologic-radiomics model may be useful for the preoperative assessment of postsurgical outcomes in patients with mass-forming intrahepatic cholangiocarcinoma.
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